The authors undertook a meta analysis of nine randomized clinical trials (RCTs) in which modified amino acid solutions that contained supplemental amounts of branched-chain amino acids (BCAA) were compared with other forms of therapy of hepatic encephalopathy (HE). When five RCTs were pooled, analysis showed highly significant improvement in the degree of HE (p < 0.001). Various interpretations of the data gave similar results. The mortality data differed so widely in these RCTs that pooling of the data could not be meaningfully performed. In two RCTs BCAA therapy resulted in increased mortality, whereas in two others BCAA treatment was associated with increased survival. An aggregate relative risk reduction of 0.59 was calculated with 95% confidence intervals of 0.23 to 0.80 (p < 0.002). When the data from one additional study that had not yet been published and that showed BCAA therapy to be beneficial was added to the analysis, the pooled relative reduction was even greater (i.e., 0.82 [p < 0.00011). The mortality in these studies was significantly reduced regardless of the type of statistical analysis performed (p = 0.023). Nevertheless, because of the short duration of follow-up in these studies and the striking differences in the effects of BCAA on mortality, the authors recommended that additional RCTs with prolonged follow-up be performed.
COMMENTS
Meta-analysis is a general term to describe the statistical analysis of a group of results of individual investigations for the purpose of integrating the findings. Since they allow for the quantitative synthesis of all available findings, such analyses in clinical trials offer an attractive approach to strengthen the evidence about the efficacy of treatment and are, therefore, popular in the medical literature. The approach is especially advantageous when the individual trials are either too small or yield inconsistent conclusions about the effect of treatment.